The Regulation of Fibroblast to Myofibroblast Activation by Zinc Finger E‐Box Binding Homeobox 1 and 2
Bibliographic record
Abstract
After a myocardial infarction (MI), a dense collagen scar is formed that initially prevents the heart from rupturing. However, after the scar is formed, collagen deposits accumulate and the extracellular matrix (ECM) is remodeled in the viable areas of the heart, distal from the site of injury, which causes the entire organ to vstiffen in a process called cardiac fibrosis (CF). CF often contributes to the development of heart failure (HF) which is a major clinical problem in Canada. Cardiac fibroblasts (FBs) provide structural support and remodel the ECM in the healthy heart, but after an MI, FBs become activated, proliferate, and adopt a myofibroblast (MF) phenotype. MFs can continue to produce ECM long after they become activated which leads to CF and ultimately HF. Two transcription factors that have been identified as potential contributors to CF are zinc finger E‐box binding homeobox 1 and 2 (ZEB1/2). ZEB1 and ZEB2 are essential for epithelial‐mesenchymal transition (EMT) and, previous studies in our lab have shown that ZEB2 is also directly involved with FB activation. Based on other research we hypothesize that ZEB1 may also regulate FB activation and be functionally redundant with ZEB2. Our initial results show that ZEB1 protein and RNA levels both increase as FBs convert to MFs. By comparing samples at varying time points we have increased our understanding of the FB to MF activation process. This study show that ZEB1 may be involved in the fibrotic process and further analysis will determine the extent of its involvement. Support or Funding Information Supported by a grant from NSERC and from the St. Boniface Hospital Foundation Research without Borders initiative.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".